Is CDON p.Pro35fs (c.101dup) pathogenic?

CDON p.Pro35fs (c.101dup) is classified Uncertain significance in CDON (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-31). No gnomAD frequency available for this variant; Associated with holoprosencephaly 11.

What condition is associated with CDON p.Pro35fs (c.101dup)?

CDON p.Pro35fs (c.101dup) is associated with holoprosencephaly 11 (ClinVar).

How common is CDON p.Pro35fs (c.101dup) in the general population?

CDON p.Pro35fs (c.101dup) is no gnomAD frequency available for this variant (gnomAD).

CDON p.Pro35fs

c.101dup · rs2497264613 · VCV2439888

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

holoprosencephaly 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP 0.52, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CDON
Protein: p.Pro35fs
Coding: c.101dup
MANE Select: NM_001378964
dbSNP: rs2497264613
Type: Duplication
Location: chr11:126021495 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 3 PDB
Residue 35: the ig-like c2-type 1 domain

Full CDON gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

holoprosencephaly 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDON p.Gln587fs Uncertain significance ★ same condition
CDON p.Leu8_Cys9insLeu Uncertain significance ★ same condition
CDON p.Pro35Ser Uncertain significance ★ ⚠ same residue
CDON c.3276+1G>T Uncertain significance ★★ same condition
CDON c.640+1G>A Uncertain significance ★★ same condition
CDON c.*1805A>G Uncertain significance ★★ same condition
CDON c.*1816C>T Uncertain significance ★★ same condition
CDON c.*2349A>C Uncertain significance ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cdon-p-pro35fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown